Enantioselective radical cyclisation reactions of 4-substituted quinolones mediated by a chiral template

Abstract

Six 4-substituted quinolones 6–8, which bear an ω-iodoalkyl chain, were prepared and subjected to reductive radical cyclisation conditions employing BEt₃/O₂ as the initiator and either Bu₃SnH or TMS₃SiH as hydride source. 4-(4-Iodobutyl)-quinolone (6a) and 4-(3-iodopropylthio)-quinolone (8a) gave the respective 6-endo-cyclisation products in good yields. 4-(3,3-Dimethyl-4-iodobutyl)-quinolone (6b) cyclised in a 5-exo-fashion, while the other substrates delivered only reduction products. The cyclisation reactions could be conducted in the presence of a chiral template (1) with high enantiomeric excess (94–99% ee). The association behaviour of substrate 6a to 1 was studied by NMR titration experiments. In the enantioselective cyclisation of 6b a significant nonlinearity was observed when comparing the product ee with the ee of the template.